MELPHALAN Film-coated tablets Ref.[8200] Active ingredients: Melphalan

Absorption

The absorption of oral melphalan is highly variable with respect to both the time to first appearance of the drug in plasma and peak plasma concentration.

In studies of the absolute bioavailability of melphalan the mean absolute bioavailability ranged from 56 to 85%.

Intravenous administration can be used to avoid variability in absorption associated with myeloablative treatment.

In a study of 18 patients administered melphalan 0.2 to 0.25 mg/kg bodyweight orally, a maximum plasma concentration (range 87 to 350 nanograms/ml) was reached within 0.5 to 2.0 h.

The administration of melphalan tablets immediately after food delayed the time to achieving peak plasma concentrations and reduced the area under the plasma concentration-time curves by between 39 and 45%.

Distribution

Melphalan displays limited penetration of the blood-brain barrier. Several investigators have sampled cerebrospinal fluid and found no measurable drug. Low concentrations (~10% of that in plasma) were observed in a single high-dose study in children.

Elimination

In 13 patients given oral melphalan at 0.6 mg/kg bodyweight, the plasma mean terminal elimination half-life was 90 ± 57 min with 11% of the drug being recovered in the urine over 24 h.

In 18 patients administered melphalan 0.2 to 0.25 mg/kg bodyweight orally, the mean elimination half-life was 1.12 ± 0.15 h.

Special Patient Populations

Renal impairment

Melphalan clearance may be decreased in renal impairment (see Dosage and Administration – Renal impairment and Warnings and Precautions – Renal impairment).

Elderly

No correlation has been shown between age and melphalan clearance or with melphalan terminal elimination half-life (see Dosage and Administration).

There are no preclinical data of relevance to the prescriber, which are additional to that in other sections of the SmPC.